Lamellar Nanoporous Metal/Intermetallic Compound Heterostructure Regulating Dendrite-Free Zinc Electrodeposition for Wide-Temperature Aqueous Zinc-Ion Battery.

Aqueous zinc-ion batteries are attractive post-lithium battery technologies for grid-scale energy storage because of their inherent safety, low cost and high theoretical capacity. However, their practical implementation in wide-temperature surroundings persistently confronts irregular zinc electrodeposits and parasitic side reactions on metal anode, which leads to poor rechargeability, low Coulombic efficiency and short lifespan. Here, this work reports lamellar nanoporous Cu/Al2Cu heterostructure electrode as a promising anode host material to regulate high-efficiency and dendrite-free zinc electrodeposition and stripping for wide-temperatures aqueous zinc-ion batteries. In this unique electrode, the interconnective Cu/Al2Cu heterostructure ligaments not only facilitate fast electron transfer but work as highly zincophilic sites for zinc nucleation and deposition by virtue of local galvanic couples while the interpenetrative lamellar channels serving as mass transport pathways. As a result, it exhibits exceptional zinc plating/stripping behaviors in aqueous hybrid electrolyte of diethylene glycol dimethyl ether and zinc trifluoromethanesulfonate at wide temperatures ranging from 25 to -30 °C, with ultralow voltage polarizations at various current densities and ultralong lifespan of >4000 h. The outstanding electrochemical properties enlist full cell of zinc-ion batteries constructed with nanoporous Cu/Al2Cu and ZnxV2O5/C to maintain high capacity and excellent stability for >5000 cycles at 25 and -30 °C.

Contributions and Prognostic Values of N6-Methyladenosine RNA Methylation Regulators in Hepatocellular Carcinoma.

INTRODUCTION: The methylation at position N6 of adenine is called N6-methyladenosine (m6A). This transcriptional RNA modification exerts a very active and important role in RNA metabolism and in other biological processes. However, the activities of m6A associated with malignant liver hepatocellular carcinoma (LIHC) are unknown and are worthy of study. MATERIALS AND METHODS: Using the data of University of California, Santa Cruz (UCSC), the expression of M6A methylation regulators in pan-cancer was evaluated as a screening approach to identify the association of M6A gene expression and 18 cancer types, with a specific focus on LIHC. LIHC datasets of The Cancer Genome Atlas (TCGA) were used to explore the expression of M6A methylation regulators and their clinical significance. Gene Ontology (GO) analysis and Gene Set Enrichment Analysis (GSEA) were used to explore the underlying mechanism based on the evaluation of aberrant expression of m6A methylation regulators. RESULTS: The expression alterations of m6A-related genes varied across cancer types. In LIHC, we found that in univariate Cox regression analysis, up-regulated m6A modification regulators were associated with worse prognosis, except for ZC3H13. Kaplan-Meier survival curve analysis indicated that higher expression of methyltransferase-like protein 3 (METTL3) and YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) genes related to the worse survival rate defined by disease-related survival (DSS), overall survival (OS), progression-free interval (PFI), and disease-free interval (DFI). Up-regulated m6A methylation regulator group (cluster2) obtained by consensus clustering was associated with poor prognosis. A six-gene prognostic signature established using the least absolute shrinkage and selection operator (LASSO) Cox regression algorithm performed better in the early (I + II; T1 + T2) stages than in the late (III + IV; T3 + T4) stages of LIHC. Using the gene signature, we constructed a risk score and found that it was an independent predictive factor for prognosis. Using GSEA, we identified processes involved in DNA damage repair and several biological processes associated with malignant tumors that were closely related to the high-risk group. CONCLUSION: In summary, our study identified several genes associated with m6A in LIHC, especially METTL3 and YTHDF1, and confirmed that a risk signature comprised of m6A-related genes was able to forecast prognosis.

Ascorbic acid decreases the antifungal effect of fluconazole in the treatment of candidiasis.

1. The aim of the present study was to investigate the effects of ascorbic acid (AA) on the antifungal activity of fluconazole (FCZ) in a systemic murine candidiasis model as well as in vitro. 2. The murine model was established by infusion of Candida albicans via the tail vein. Control mice received no further treatment. Other groups of mice were injected with FCZ (0.5 mg/kg, i.p.) and then treated or not with 50 or 500 mg/kg AA intragastrically (i.g.) or i.p. In all groups, FCZ was administered i.p. 2 h after fungal inoculation, whereas AA was administered 6 h after fungal inoculation. Survival rate, kidney fungal burden and renal pathological changes were evaluated. 3. The in vitro effects of AA (5, 1 and 0.2 mmol/L) on the growth of various Candida strains in the presence of FCZ (0.125-64 microg/mL) were also investigated. The in vitro effects of two anti-oxidants, namely N-acetylcysteine (NAC; 5, 1 and 0.2 mmol/L) and reduced glutathione (GSH; 5, 1 and 0.2 mmol/L), on FCZ activity were evaluated to determine the mechanism of action of AA. 4. Intragastric administration of AA (50 or 500 mg/kg) significantly decreased the antifungal effect of 0.5 mg/kg FCZ. Although i.p. administration of AA (50 or 500 mg/kg) had no significant effect on the survival of mice, it dose-dependently inhibited the activity of FCZ, with significant inhibition observed with 500 mg/kg AA. 5. In vitro, AA decreased the activity of FCZ against various Candida strains. Both NAC and GSH dose-dependently decreased the activity of FCZ. 6. The results of the present study indicate that AA inhibits the antifungal activity of FCZ, suggesting that the two should not be used together clinically for the treatment of candidiasis.

Andrographolide suppresses proliferation of human colon cancer SW620 cells through the TLR4/NF-κB/MMP-9 signaling pathway.

Modern pharmacological research has revealed that andrographolide has various functions, including anti-bacterial, anti-inflammatory and anti-viral effects, immunoregulation, treating cardiovascular and cerebrovascular diseases, and prevention and treatment of alcoholic liver injury. The present study investigated whether andrographolide suppresses the proliferation of human colon cancer cell through the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB/matrix metalloproteinase-9 (MMP-9) signaling pathway. The MTT assay and lactate dehydrogenase assay were used to evaluate the anticancer effects of andrographolide on cell proliferation and cytotoxicity in human colon cancer SW620 cells. Flow cytometry was used to analyze the anticancer effects of andrographolide on apoptosis by Annexin V-fluorescein isothiocyanate/propidium iodide kit. The effects of andrographolide on the activity of caspase-3/9 were measured using ELISA. Western blot analysis was also used to analyze the protein expression of TLR4, myeloid differentiation primary response gene 88 (MyD88), NF-κB-p65 and MMP-9. In the present study, it was found that andrographolide suppressed the cell proliferation, augmented cytotoxicity, evoked cell apoptosis and activated caspase-3/9 activities in human colon cancer SW620 cells. The results revealed that the anti-proliferation effects of andrographolide on the SW620 cells was associated with the inhibition of TLR4, MyD88, NF-κB-p65 and MMP-9 signaling activation. The results suggest that andrographolide is a promising drug for treatment of human colon cancer via suppression of the TLR4/NF-κB/MMP-9 signaling pathway.

CaIPF7817 is involved in the regulation of redox homeostasis in Candida albicans.

CaIPF7817, a functionally unknown gene in Candida albicans, was suggested to be involved in the redox system previously, but its exact role is unknown. In this study, ipf7817 null mutant was generated with the URA-blaster method. After the deletion of CaIPF7817, intracellular levels of reactive oxygen species were significantly increased; mitochondrial membrane potential, a direct indicator of mitochondrial function, was elevated; some important redox-related genes, including GLR1, SOD2, and TRR1, were up-regulated; and the GSH/GSSG ratio was raised. These changes indicated that CaIPF7817 played important roles in the regulation of redox homeostasis in C. albicans.